PCL201H1 Lecture Notes - Lecture 3: Biopharmaceutical, Extracellular Fluid, Bioaccumulation

23 views3 pages
14 Sep 2016
School
Course
Professor

For unlimited access to Class Notes, a Class+ subscription is required.

PCL201
Winter 2014
Lecture 3 Drugs as Molecules
1. Introduction (biological membranes and physicochemical properties of drugs)
2. Molecular size
3. Solubility (in water and lipid)
4. Ionization
1. Introduction (biological membranes and physicochemical properties of drugs)
A drug needs to exert an effect on its target (ADME)
It must be soluble in bodily fluids and cross biological membranes
In the biological membrane, epithelial cells and endothelial cells have a barrier (other
cells may have fenestrations)
Total body water include intracellular fluid, extracellular fluid, plasma, and interstitial
fluid
Properties that affect a drug’s permeability and distribution:
o Molecular size
o Solubility in water and lipid
o Extent of ionization
2. Molecular size
Expressed in Daltons (Da)
Most drugs are 200-500 Da, proteins (as well as biologics) are much larger
Small hydrophobic drugs can passively cross the biological membrane
3. Solubility (in water and lipid)
Affected by polarity and temperature
o Polar and ionic compounds dissolve in water, i.e. hydrophilic/lipophobic
Does not readily cross the membrane (increase in free energy)
o Those that dissolve in fat are hydrophobic/lipophilic
Bioaccumulation of hydrophobic molecules can occur in adipose tissues
Hydrophobic molecules more easily crosses the membrane (decrease in
free energy)*
*Too hydrophobic actually can’t cross the membrane due to the hydrophilic
barrier of the “unstirred water layer”
Polarity is largely dependent on functional groups and the type of chemical bonds
Earlier we said that drugs must be soluble in bodily fluids and cross biological
membranes, this balance is important
o Amphipathic molecules have polar and non-polar regions, so can dissolve in both
water and fat
o The partition coefficient (Pow or Kow) measures the relative affinity of a
molecule for lipid and aqueous phases
The higher the coefficient, the more hydrophobic
Unlock document

This preview shows page 1 of the document.
Unlock all 3 pages and 3 million more documents.

Already have an account? Log in

Get access

Grade+
$10 USD/m
Billed $120 USD annually
Homework Help
Class Notes
Textbook Notes
40 Verified Answers
Study Guides
1 Booster Class
Class+
$8 USD/m
Billed $96 USD annually
Homework Help
Class Notes
Textbook Notes
30 Verified Answers
Study Guides
1 Booster Class